The fast extensor digitorum longus (EDL) and the slow soleus (SOL) muscles were cross-reinnervated in both directions in the rat. During the following transformation of muscle type properties, the expression of the Ca2+-binding parvalbumin (parvalbumin, Mr = 12,000) was investigated. The combined biochemical, histochemical, and physiological results demonstrated that the amount of parvalbumin decreased in the fast to slow (X-EDL) and increased in the slow to fast (X-SOL) transformation. Alterations of parvalbumin-mRNA levels were similar to changes found at the protein level, indicating a tight transcriptional regulation of the parvalbumin expression. The close correlation, however, between parvalbumin and relaxation speed found in normal muscles had changed after cross-reinnervation. After the altered nervous input, a slow contracting/slow relaxing muscle may even contain more parvalbumin than a fast contracting/fast relaxing one. The expression of parvalbumin may depend on the nerve-muscle interaction, and parvalbumin may thus be used as a sensitive marker for early stages of muscular transformation and neurological disorders.